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Treatment of hypertension; management of ventricular arrhythmias
The 2014 guideline for the management of high blood pressure in adults (Eighth Joint National Committee [JNC 8; James, 2013]) recommends initiation of pharmacologic treatment to lower blood pressure for the following patients:
- Patients ≥60 years of age with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg. Goal of therapy is SBP <150 mm Hg and DBP <90 mm Hg.
- Patients <60 years of age with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
- Patients ≥18 years of age with diabetes and SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
- Patients ≥18 years of age with chronic kidney disease (CKD) and SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
In patients with CKD, regardless of race or diabetes status, the use of an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) as initial therapy is recommended to improve kidney outcomes. In the general nonblack population (without CKD), including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic, calcium channel blocker, ACEI, or ARB. In the general black population (without CKD), including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic or a calcium channel blocker instead of an ACEI or ARB.
Overt cardiac failure; cardiogenic shock; persistently-severe bradycardia or second- and third-degree heart block (except in patients with a functioning artificial pacemaker)
Angina, ventricular arrhythmia: Oral: 400 mg/day in 2 divided doses; maintenance: 600 to 1200 mg/day in divided doses; maximum: 1200 mg/day
Hypertension: Oral: Initial: 400 mg in 1 to 2 divided doses; optimal response usually seen at 400 to 800 mg daily (larger doses may be divided) although some patients may respond to as little as 200 mg daily; usual dose range (ASH/ISH [Weber, 2014]): 200 to 400 mg daily; maximum dose: 1200 mg in 2 divided doses
Chronic stable angina (off-label use): Oral: Usual dose: 400 to 1200 mg/day in 2 divided doses (Gibbons, 2003); low doses (ie, 400 mg/day) may also be given as once daily (Pina, 1988)
Refer to adult dosing. Consider dose reduction due to age-related increase in bioavailability; do not exceed 800 mg/day. In the management of hypertension, consider lower initial dose (eg, 200 to 400 mg/day) and titrate to response (Aronow, 2011).
CrCl 25 to 49 mL/minute: Reduce dose by 50%.
CrCl <25 mL/minute: Reduce dose by 75%.
There are no dosage adjustments provided in manufacturers labeling; use with caution.
May be administered without regard to meals.
May be taken without regard to meals.
Store at controlled room temperature of 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F). Protect from light and dispense in a light-resistant, tight container.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as hydrochloride:
Sectral: 200 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #6 (sunset yellow)]
Sectral: 400 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, fd&c yellow #6 (sunset yellow)]
Generic: 200 mg, 400 mg
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Alpha-/Beta-Agonists (Direct-Acting): Beta-Blockers may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Some beta-adrenoceptor mediated effects of Alpha-/Beta-Agonists (Direct-Acting), including anti-anaphylactic effects of epinephrine, may be diminished by Beta-Blockers. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Exceptions: Dipivefrin. Consider therapy modification
Alpha1-Blockers: Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Monitor therapy
Alpha2-Agonists: May enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Exceptions: Apraclonidine. Consider therapy modification
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. Monitor therapy
Amiodarone: May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Monitor therapy
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Anilidopiperidine Opioids: May enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Barbiturates: May decrease the serum concentration of Beta-Blockers. Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Beta2-Agonists: Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Monitor therapy
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy
Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil. Monitor therapy
Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Avoid combination
Cholinergic Agonists: Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Management: Administer these agents in combination with caution, and monitor for conduction disturbances. Avoid methacholine with any beta blocker due to the potential for additive bronchoconstriction. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. Monitor therapy
Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Consider therapy modification
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy
Ergot Derivatives: Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline. Consider therapy modification
Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and beta-blockers if possible. If coadministration is necessary, patients should have overnight continuous ECG monitoring conducted after the first dose of fingolimod. Monitor patients for bradycardia. Consider therapy modification
Floctafenine: May enhance the adverse/toxic effect of Beta-Blockers. Avoid combination
Grass Pollen Allergen Extract (5 Grass Extract): Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Insulin: Beta-Blockers may enhance the hypoglycemic effect of Insulin. Monitor therapy
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy
Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy
Lidocaine (Systemic): Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). Monitor therapy
Lidocaine (Topical): Beta-Blockers may increase the serum concentration of Lidocaine (Topical). Monitor therapy
Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Avoid combination
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Midodrine: Beta-Blockers may enhance the bradycardic effect of Midodrine. Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
NIFEdipine: May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Regorafenib: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Reserpine: May enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Monitor therapy
Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Avoid combination
Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy
Sulfonylureas: Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Monitor therapy
Theophylline Derivatives: Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Theophylline Derivatives. Management: Monitor for reduced theophylline efficacy during concomitant use with any beta-blocker. Beta-1 selective agents are less likely to antagonize theophylline than nonselective agents, but selectivity may be lost at higher doses. Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Blood glucose (especially in patients with diabetes mellitus); blood pressure, orthostatic hypotension, heart rate, CNS effects, ECG
>10%: Central nervous system: Fatigue (11%)
1% to 10%:
Cardiovascular: Chest pain (2%), edema (2%), bradycardia, congestive heart failure, hypotension
Central nervous system: Dizziness (6%), headache (6%), insomnia (3%), abnormal dreams (2%), depression (2%), anxiety, hyperesthesia, hypoesthesia
Dermatologic: Skin rash (2%), pruritus
Gastrointestinal: Constipation (4%), diarrhea (4%), dyspepsia (4%), nausea (4%), flatulence (3%), abdominal pain, vomiting
Genitourinary: Urinary frequency (3%), dysuria, impotence, nocturia
Neuromuscular & skeletal: Myalgia (2%), arthralgia, back pain
Ophthalmic: Visual disturbance (2%), conjunctivitis, dry eye syndrome, eye pain
Respiratory: Dyspnea (4%), rhinitis (2%), cough (1%), pharyngitis, wheezing
<1% (Limited to important or life-threatening): Anorexia, atrioventricular block, cold extremities, drug-induced lupus-like syndrome, exacerbation of renal insufficiency, facial edema, hepatotoxicity, increased serum alkaline phosphatase, increased serum bilirubin, increased serum transaminases, lichen planus, palpitations, pleurisy, pneumonitis, pulmonary granuloma, systemic lupus erythematosus, urinary retention, ventricular arrhythmia, xerostomia
Decreased elimination of diacetolol resulting in a 2- to 3-fold increase in its half-life.
Bioavailability increased about 2-fold.
Concerns related to adverse events:
- Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
Disease-related concerns:
- Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; for patients with bronchospastic disease who do not respond to or cannot tolerate other therapies, initial low doses of acebutolol may be employed and used cautiously with close monitoring. Ensure patient has an inhaled beta2-agonist immediately available.
- Conduction abnormality: Consider preexisting conditions such as sick sinus syndrome before initiating.
- Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.
- Heart failure (HF): Beta-blockers with intrinsic sympathomimetic activity (eg, acebutolol) are likely to worsen survival in patients with HF and should be avoided. Beta-blockers shown to improve survival in clinical trials should be used in these patients.
- Hepatic impairment: Use with caution in patients with hepatic impairment.
- Mesenteric vascular disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with mesenteric vascular disease. Use with caution in these patients. Observe closely for progression of arterial obstruction.
- Myasthenia gravis: Use with caution in patients with myasthenia gravis.
- Peripheral vascular disease (PVD) and Raynauds disease: May precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud's disease. Use with caution and monitor for progression of arterial obstruction.
- Pheochromocytoma (untreated): Adequate alpha1-receptor blockade is required prior to use of any beta-blocker.
- Psoriasis: Beta-blocker use has been associated with induction or exacerbation of psoriasis, but cause and effect have not been firmly established.
- Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression.
- Renal impairment: Use with caution in patients with renal impairment, especially the elderly. Elimination of the metabolite, diacetolol, is reduced resulting in a two- to threefold increase in its half-life.
- Thyroid disease: May mask signs of hyperthyroidism (eg, tachycardia). If hyperthyroidism is suspected, carefully manage and monitor; abrupt withdrawal may precipitate thyroid storm. Alterations in thyroid function tests may be observed.
Concurrent drug therapy issues:
- Calcium channel blockers: Use with caution in patients on concurrent verapamil or diltiazem; bradycardia or heart block can occur.
- Cardiac glycosides: Use with caution in patients receiving digoxin; bradycardia or heart block can occur.
- Inhaled anesthetic agents: Use with caution in patients receiving inhaled anesthetic agents known to depress myocardial contractility.
Special populations:
- Elderly: Use reduced doses in elderly patients; concentrations of acebutolol and diacetolol are significantly higher in the elderly. Dose should not exceed 800 mg/day.
Other warnings/precautions:
- Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia. Severe exacerbation of angina, ventricular arrhythmias, and myocardial infarction (MI) have been reported following abrupt withdrawal of beta-blocker therapy. Temporary but prompt resumption of beta-blocker therapy may be indicated with worsening of angina or acute coronary insufficiency.
- Major surgery: Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.
B
Adverse effects were observed in some animal reproduction studies. Acebutolol and diacetolol (active metabolite) cross the placenta. Decreases in birth weight, blood pressure, and heart rate have been observed in neonates following maternal use of acebutolol during pregnancy. Hypoglycemia has also been found following in utero exposure to beta-blockers as a class. The half-life of acebutolol is 6 to 14 hours in the newborn. The half-life of diacetolol is 24 to 30 hours for the first 24 hours of life, then 12 to 16 hours. Adequate facilities for monitoring infants at birth should be available. The plasma elimination half-life of acebutolol is longer in pregnant women at term (Bianchetti 1981a; Boutroy 1982).
Untreated chronic maternal hypertension and preeclampsia are also associated with adverse events in the fetus, infant, and mother (ACOG 2015; Magee 2014). When treatment of hypertension in pregnancy is indicated, beta-blockers may be used. Specific recommendations vary by guideline. Although other agents are preferred (ACOG 2013), use of acebutolol may be considered (Magee 2014).
Competitively blocks beta1-adrenergic receptors with little or no effect on beta2-receptors except at high doses; exhibits membrane stabilizing and intrinsic sympathomimetic activity
Oral: 40%
Vd: 1.2 L/kg
Extensive first-pass effect to equipotent and cardioselective diacetolol metabolite
Feces (50% to 60%); urine (30% to 40%); diacetolol eliminated primarily in the urine
1 to 2 hours
2 to 4 hours
12 to 24 hours
Parent drug: 3 to 4 hours; Metabolite: 8 to 13 hours
~26%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache or loss of strength and energy. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), severe dizziness, passing out, shortness of breath, excessive weight gain, swelling of arms or legs, bradycardia, or abnormal heartbeat (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.